This report describes characterization of the fly alcohol response using the Drosophila gene GstO1. Dmel\GstO1 encodes a cytoplasmic glutathione S-transferase of the omega class. The single fly gene is orthologous to 2 genes in human, GSTO1 and GSTO2. RNAi targeting constructs and an allele caused by insertional mutagenesis have been generated for Dmel\GstO1.
The human genes Hsap\GSTO1 and Hsap\GSTO2 have been introduced into flies, but have not been characterized.
Animals homozygous for a loss-of-function Dmel\GstO1 mutation exhibit highly increased ethanol sensitivity (decreased resistance to ethanol-induced sedation). GstO1 overexpression in wild-type animals results in increased resistance to ethanol compared to the control. Neural expression of GstO1 plays a major role in these effects: sensitivity to ethanol-induced sedation is strongly increased when GstO1 is reduced via RNAi in most dopaminergic and serotonergic neurons.
[updated May 2019 by FlyBase; FBrf0222196]
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
GSTO1 and GSTO2 encode omega class glutathione S-transferases (GSTs) with glutathione-dependent thiol transferase and dehydroascorbate reductase activities. GSTs are involved in the metabolism of xenobiotics and carcinogens. [Gene Cards, GSTO1, GSTO2; 2019.05.02]
Glutathione S-transferases (GST) are a family of enzymes that catalyze conjugation of reduced glutathione to a wide range of substrates, usually resulting in detoxification. They also function as transport proteins. (https://www.sciencedirect.com/topics/neuroscience/glutathione-s-transferase)
Many to one: 2 human to 1 Drosophila.
Many to one: 2 human to 1 Drosophila.
Moderate- to high-scoring ortholog of human GSTO1 and GSTO2 (1 Drosophila to 2 human). Dmel\GstO1 shares 33-37% identity and 48-50% similarity with the human genes.
